Episode 65: This episode covers atrophy, hypertrophy, metaplasia, dysplasia, and hyperplasia.

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Adaptations to environmental stress: Growth alterations

A. Atrophy:

Diagnosis: the decrease in tissue mass and the cell decreases in size. The cell has just enough organelles to survive, ie less mitochondria then normal cells, therefore, just trying to ‘eek’ it out until whatever it needs to stimulate can come back.

1. Example: hydronephrosis, the compression atrophy is causing thinning of cortex and medulla, MCC hydronephrosis is stone in the ureter (the pelvis is dilated). Question can be asked what kind of growth alteration can occur here. Answer is atrophy b/c of the increased pressure on the cortex and the medulla and produces to ischemia, blood flow decreases and can produce atrophy of renal tubules.

2. Example: Atrophied brain due to atherosclerosis (MC) or degeneration of neurons (Alzheimers, related to beta amyloid protein, which is toxic to neurons).

3. Example: In muscle, many causes of atrophy – ie Lou Gehrig’s Dz (amyotrophic lateral sclerosis) knock off neurons to the muscle, so it is not stimulated, leading to atrophy.

4. Example: Endocrine related:

a) Hypopituitarism will lead to atrophy of adrenal cortex: the zona fasiculata and retiucularis layers of the adrenal cortex; NOT the glomerulosa b/c ACTH has nothing to with stimulating aldosterone release. The fasiculata is where glucocorticoids (cortisol) are made, while reticularis is where sex hormones are made (17 ketosteroids and testosterone). ACTH is responsible for stimulating these, therefore zona fasiculata and zona reticularis are atrophied.

b) Taking thyroid hormone will lead to atrophy of thyroid gland. This is due to a decrease of TSH and therefore nothing is stimulating the thyroid gland which leads to atrophy.

5. Example: Slide showing a biopsy of a pancreas in a patient with cystic fibrosis. What is growth alteration? Atrophy, b/c the CFTR regulator on c’some 7 is defective and has problems with secretions. The secretions become thicker and as a result, it blocks the ducts and so that means that the glands that were making the fluids (the exocrine part of the gland) cannot make fluids b/c of the back pressure blocking the lumen of the duct, which leads to atrophy of the glands, which then leads to malabsorption in all children with cystic fibrosis.

6. Example: Slide of an aorta, with atherosclerotic plaque, which leads to atrophy of the kidney and secondary HTN (renovasuclar HP, leading to high renin level coming out of the kidney). In the other kidney, it is overworked, therefore there is hypertrophy (renin level coming out of this vein is decreased and suppressed).

B. Hypertrophy

Increase of the SIZE of cell, not number Scenario: A cell biology question: what is the N of this? Hypertrophy of a cardiac muscle (permanent muscle), suppose there is a block just before the G2 phase. What is the number of chromosomes? Answer: # of c’somes is 4N, b/c it already underwent synthesis: already doubled.

1 N = sperm (23 c’somes)

2 N = normal (diploid cell)

3 N = trisomy

4 N = double the number

C. Hyperplasia

Increase in the # of cells. In normal proliferative gland, there are thousands of mitoses, therefore see more glands with hyperplasia.

1. Example leading to cancer: With unopposed estrogen, you may end up with cancer, b/c if you didn’t have progesterone (undoes what estrogen did-counteracts the estrogen), you will get cancer. The cells will go from hyperplasia, to atypical hyperplasia to endometrial cancer. Therefore hyperplasia left unchecked there is an increased risk of cancer. One exception: benign prostatic hyperplasia; hyperplasia of the  prostate does NOT lead to cancer; just urinary incontinence.

2. Example: gravid uterus (woman’s uterus after delivery). This is an example of 50:50: 50% hypertrophy of the smooth muscle cells in the wall of the uterus, and 50% related to hyperplasia.

3. Example: Bone marrow: normally should have 3X as many WBC’s as RBC’s. Slide shows few WBC’s, and increased RBC’s. Therefore, have RBC hyperplasia. This is not expected to be seen in Iron def anemia nor in thalassemias b/c in those, there a defect in Hb production. It is expected to be seen in chronic obstructive pulmonary dz (COPD) b/c the hypoxemia causes the release of hormone EPO (erythropoietin); which is made in the endothelial cells of the peritubular capillaries. So in the slide this is an example of EPO stimulated marrow.

4. Example: psoriasis on elbow –an example of hyperplasia (unregulated proliferation of squamous cells in the skin), leading to red skin, and raised red plaque, b/c excessive stratum corneum. This is why methotrexate works here, b/c it’s a cell cycle specific for the S phase, and prevents the basal cells from proliferating.

5. Example: prostate gland and bladder – hyperplasia of prostate glands, it a hormone related hyperplasia; all hormone stimulated glands undergo hyperplasia, not hypertrophy. The wall of the bladder is too thick; b/c urine has to go out thru a narrow opening in the urethra, therefore the muscle has to work harder which leads to hypertrophy of smooth muscle cells of the bladder wall (more urine must go out against a greater force b/c of an increase in after load).

D. Metaplasia

Replacement of one adult cell type by another.

1. Example: Slide of an esophagus, part of if is all ulcerated away. On a section surrounding the ulcer (right at the edge of the muscosa) there are mucous secreting cells and goblet cells (these are grandular cells). These cells are not supposed to be present in lower esophagus; squamous cells should be there (not glandular cells). Metastatic grandular: Barrets esophagus is a precursor for adenocarcinoma. Adenocarcinoma has surpassed squamous cell carcinoma of mid-esophagus as the MC cancer of the esophagus. Therefore, GERD is the number one precursor to esophageal cancer (adenocarcinoma).

2. Example: Lining of mainstem bronchus – ciliated columnar, pseudostatified columnar. In smokers, this would be an example of metaplasia would be squamous.

3. Example: There are increased goblet cells within mainstem bronchus of an old smoker, also see goblet cells in the terminal bronchial. Normally there are goblet cells in the mainstem bronchus but there are no goblet cells in the terminal bronchus, therefore this is an example of metaplasia.

4. Example: Goblet cells in the stomach are abnormal (should be in the intestines, only). This is a glandular metaplasia, which is a precursor for adenocarcinoma of the stomach. H. pylori are a precursor for adenocarcinoma in the stomach. B/c H. pylori causes damage to pylorus and antral mucosa b/c it is a chronic gastritis which intestinal glandular metaplasia, which is a precursor for adenocarcinoma. MCC  adenocarcinoma of the stomach = H. pylori.

5. Example: Cases where metaplasia causes an increased risk of cancer:

a) Remember that if hyperplasia is left unchecked, could potentially lead to cancer. For example: in endometrial hyperplasia the MC precursor lesion to endometrial carcinoma due to unopposed estrogen. The exception is prostatic hyperplasia, which doesn’t become cancer.

b) Metaplasia can also go through a process leading to cancer:

(1) In lung, ciliated columnar epithelium BECOMES squamous, therefore, this is called SQUAMOUS metaplasia; this will lead to squamous dysplasia, which then proceeds to cancer (squamous carcinoma);

(2) In distal esophagus, went from squamous to glandular epithelium b/c squamous epithelium cannot handle the acid, therefore it needs mucous secreting epithelium as a defense against cellular injury.  However, the glandular metaplasia can go on to an atypical metaplasia, predisposing to adenocarcinoma of the distal esophagus.

(3) Parasites: 2 parasites produce cancer: Clonesis sinesis leads to cholangiocarcinoma (Chinese liver fluke); and Shistosoma hematoabia. The Schistosomias hematobia causes bladder cancer by causing the transitional epithelium to undergo squamous metaplasia. This leads to squamous dysplasia, and then on to squamous cancer. Transitional epithelium leads to squamous epithelium (called metaplasia), then dysplasia, then on to cancer.

E. Dysplasia

Is really an atypical hyperplasia.

1. Example: Slide of a squamous epithelium is disorganized, with nuclei that are larger near the surface and the basal cell layer is responsible for the dividing; cells at top are bigger than the ones that are dividing, it has lack orientation. If it was found during a cervical biopsy in pt with HPV infection, or if it was found in the mainstem bronchus biopsy, you should be able to tell that it is dysplastic. Therefore dysplasia,  whether glandular or squamous, is a precursor for cancer.

2. Example: There was a farmer with lesion on the back of his neck (can grow on any part of the body, due to sun exposure), which could be scraped off and grew back – actinic keratosis (aka solar keratosis) – is a precursor for sq. cell carcinoma of the skin. UV-b light damages the skin. Actinic keratosis does not predispose to basal cell carcinoma, even though basal cell carcinoma is the most common skin cancer.

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